Physical Sciences, Inc. (PSI), in collaboration with Memorial Sloan Kettering Cancer Center (MSKCC) and Caliber Imaging & Diagnostics Inc. (Caliber ID), proposes to develop a hand-held reflectance confocal microscopy - optical coherence tomography (RCM-OCT) imaging probe and clinically evaluate its potential use for guiding laser ablation therapy of BCC basal cell carcinoma (BCC). While RCM provides en face images with nuclear-level resolution in superficial skin, to depths of about 200 m, OCT provides cross-sectional images with structural-level resolution in the deeper skin layers, to depths of at least 1 mm. The complementary capabilities of these two optical technologies may be exploited to aid BCC laser ablation therapy. Laser ablation is particularly effective for minimally invasive removal of superficial and early nodular BCCs. Superficial and early nodular BCCs constitute about 40% (600,000 per year) of Mohs surgical cases. Skin can be removed in m-thin layers in a highly controlled manner. However, tissue is vaporized during ablation such that there is none available for immediate pathological evaluation for the presence or clearance of tumor. The lack of pathological feedback results in variable efficacy and limited cure rate. A high-resolution nuclear-level optical imaging approach with RCM and depth spreading with OCT may address this limitation by detecting the presence or clearance of residual BCCs directly on the patient, and provide immediate pathology- like feedback. Phase I study has demonstrated the suitability of combining these technologies within the same instrument, as well as the clinical value of the complimentary data. In Phase II we propose to develop a novel hand-held probe that will combine RCM and PSOCT within the same optical layout and perform its clinical evaluation for guiding laser ablation therapy of BCCs.